Resistance to cisplatin is a major obstacle to successful treatment of head and neck squamous cell carcinoma (HNSCC). To investigate the molecular mechanism of this resistance, we compared the gene expression profiles between the cisplatin-sensitive SCC cell lines (Sa-3, H-1 and KB) and the cisplatin-resistant cell lines established from them (Sa-3R, H-1R and KB-R) using Affymetrix U133 Plus 2.0 microarray. We identified 199 genes differentially expressed in each group. To identify important functional networks and ontologies to cisplatin resistance, the 199 genes were analyzed using the Ingenuity Pathway Analysis Tool. Fifty-one of these genes were mapped to genetic networks, and we validated the top-10 upregulated genes by real-time reverse transcriptase-polymerase chain reaction. Five novel genes, LUM, PDE3B, PDGF-C, NRG1 and PKD2, showed excellent concordance with the microarray data. In 48 patients with oral SCC (OSCC), positive immunohistochemical staining for the five genes correlated with chemoresistance to cisplatin-based combination chemotherapy. In addition, the expression of the five genes predicted the patient outcomes with chemotherapy. Furthermore, siRNA-directed suppressed expression of the five genes resulted in enhanced susceptibility to cisplatin-mediated apoptosis. These results suggested that these five novel genes have great potential for predicting the efficacy of cisplatin-based chemotherapy against OSCC. Global gene analysis of cisplatin-resistant cell lines may provide new insights into the mechanisms underlying clinical cisplatin resistance and improve the efficacy of chemotherapy for human HNSCC.
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Front Immunol
January 2025
School of Nursing, Zunyi Medical University, Zunyi, China.
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Department of Gynecology, Sichuan Provincial Hospital of Traditional Chinese Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People's Republic of China.
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April 2025
The First College of Clinical Medical Science, Yichang Central People's Hospital, China Three Gorges University, Yichang, 443000 China.
Despite improvements in therapeutic approaches, the mortality rate of gastric cancer (GC) remains unacceptably high. Evidence suggests that FXYD domain containing ion transport regulator 6 (FXYD6) is downregulated in GC. However, its exact function and the molecular mechanism in GC are still unclear.
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Department of Genetics, Osmania University, Hyderabad, Telangana State India.
Targeting tumor angiogenesis with safe endogenous protein inhibitors is a promising therapeutic approach despite the plethora of the first line of emerging chemotherapeutic drugs. The extracellular matrix network in the blood vessel basement membrane and growth factors released from endothelial and tumor cells promote the neovascularization which supports the tumor growth. Contrastingly, small cleaved cryptic fragments of the C-terminal non collagenous domains of the same basement membrane display antiangiogenic effect.
View Article and Find Full Text PDFCytotechnology
April 2025
University Centre for Research and Development, University Institute of Pharmaceutical Sciences, Chandigarh University, Gharuan, Mohali, 140413 India.
When juxtaposed with 2D cell culture models, multicellular tumor spheroids demonstrate a capacity to faithfully replicate certain features inherent to solid tumors. These include spatial architecture, physiological responses, the release of soluble mediators, patterns of gene expression, and mechanisms of drug resistance. The morphological and behavioural similarities between 3D-cultured cells and cells within tumor masses highlight the potential of these models in studying cancer biology and drug responses.
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